id: Q8WYP5 gene_symbol: AHCTF1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- AHCTF1 encodes ELYS/MEL-28, a large metazoan nucleoporin and chromatin-associated assembly factor for nuclear pore complexes. ELYS binds chromatin during nuclear reformation, recruits the Nup107-160/Y-complex scaffold to nascent nuclear pores, and localizes to nuclear pores, the nuclear envelope, chromatin, and kinetochores in a cell-cycle-dependent manner. Loss or perturbation of ELYS disrupts post-mitotic NPC assembly and produces chromosome segregation and cytokinesis defects, consistent with a core role in rebuilding the nuclear pore scaffold after open mitosis. alternative_products: - name: '1' id: Q8WYP5-1 - name: '2' id: Q8WYP5-2 sequence_note: VSP_019844 - name: '3' id: Q8WYP5-3 sequence_note: VSP_042691 existing_annotations: - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Nucleus is a correct but broad automated location for AHCTF1/ELYS. action: KEEP_AS_NON_CORE reason: >- AHCTF1/ELYS is consistently reported in the nucleus and nuclear envelope/nuclear pore system, but nucleus is less informative than the specific NPC, chromatin, and kinetochore locations supported by experimental evidence. additional_reference_ids: - PMID:17098863 - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0005635 label: nuclear envelope evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- Nuclear envelope is a well-supported location for AHCTF1/ELYS. action: ACCEPT reason: >- UniProt subcellular-location mapping is consistent with experimental studies showing ELYS at the nuclear envelope and nuclear pore complexes during interphase and nuclear reformation. additional_reference_ids: - PMID:17098863 - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: part_of review: summary: >- Nuclear pore is an accurate specific location for ELYS. action: ACCEPT reason: >- AHCTF1/ELYS associates with the Nup107-160/Y-complex scaffold and localizes to NPCs. This term captures the major cellular structure where the protein acts during NPC assembly and interphase NPC organization. additional_reference_ids: - PMID:17098863 - PMID:27016207 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - reference_id: PMID:17098863 supporting_text: ELYS, a putative transcription factor, was discovered to copurify with the Nup107-160 complex - term: id: GO:0005654 label: nucleoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- Nucleoplasm is supported as a reported interphase/nuclear location, but it is not the most specific functional compartment. action: KEEP_AS_NON_CORE reason: >- ELYS has nucleoplasmic signal in addition to nuclear envelope/NPC localization. Because the core role is chromatin-associated NPC assembly, nucleoplasm should be retained as a non-core location rather than used to define gene function. additional_reference_ids: - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: PMID:27341616 supporting_text: In interphase, the ratio of nucleoplasmic versus cytoplasmic GFP signal was ~4.4-fold higher for full-length MEL-28 compared to MEL-281-956_loop2m - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Cytoplasm is weakly supported by similarity and cell-cycle context but is not an informative AHCTF1 location. action: MARK_AS_OVER_ANNOTATED reason: >- The main experimental evidence places AHCTF1/ELYS at nuclear pores, nuclear envelope, chromatin, and kinetochores. Cytoplasm is at best a broad inferred or mitotic-background location and should not be propagated as a defining annotation. additional_reference_ids: - PMID:17098863 - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0016363 label: nuclear matrix evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Nuclear matrix is retained as a reported nuclear-associated location but is not central to current mechanistic evidence. action: KEEP_AS_NON_CORE reason: >- The original experimental paper and UniProt record report nuclear matrix/nuclear-associated localization, but the mechanistically informative compartments are chromatin, NPC/nuclear envelope, and kinetochore. additional_reference_ids: - PMID:17098863 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0005635 label: nuclear envelope evidence_type: IDA original_reference_id: PMID:24315095 qualifier: located_in review: summary: >- The human NPC scaffold study supports AHCTF1 as part of the nuclear pore/nuclear envelope scaffold context. action: ACCEPT reason: >- The cited structural work describes the human Nup107 scaffold of the NPC. Together with AHCTF1/ELYS evidence as a Nup107-160-associated assembly factor, nuclear envelope localization is sound. additional_reference_ids: - PMID:17098863 - PMID:27016207 supported_by: - reference_id: PMID:24315095 supporting_text: 32 copies of the Nup107 subcomplex assemble into two reticulated rings - reference_id: PMID:17098863 supporting_text: ELYS, a putative transcription factor, was discovered to copurify with the Nup107-160 complex - term: id: GO:0005643 label: nuclear pore evidence_type: NAS original_reference_id: PMID:24315095 qualifier: part_of review: summary: >- AHCTF1/ELYS is appropriately associated with the nuclear pore scaffold. action: ACCEPT reason: >- The cited structural study defines the human NPC scaffold, and independent AHCTF1 evidence shows ELYS associates with Nup107-160 and localizes to NPCs. The nuclear pore component annotation is therefore appropriate. additional_reference_ids: - PMID:17098863 - PMID:27016207 supported_by: - reference_id: PMID:24315095 supporting_text: 32 copies of the Nup107 subcomplex assemble into two reticulated rings - reference_id: PMID:17098863 supporting_text: ELYS, a putative transcription factor, was discovered to copurify with the Nup107-160 complex - term: id: GO:0006913 label: nucleocytoplasmic transport evidence_type: NAS original_reference_id: PMID:27016207 qualifier: involved_in review: summary: >- Nucleocytoplasmic transport is a real downstream function of assembled NPCs, but it is too broad for AHCTF1 itself. action: MODIFY reason: >- AHCTF1/ELYS acts primarily as a chromatin-associated initiator/scaffold for post-mitotic NPC assembly. The better direct BP annotation is nuclear pore complex assembly rather than the generic transport process carried out by the assembled pore and transport receptors. proposed_replacement_terms: - id: GO:0051292 label: nuclear pore complex assembly additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:27016207 supporting_text: The nuclear pore complex (NPC) is the principal gateway for molecular exchange between nucleus and cytoplasm - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: >- Nucleoplasm is compatible with reported ELYS localization but is not the most specific site of action. action: KEEP_AS_NON_CORE reason: >- Human and ortholog evidence shows nucleoplasmic signal, but AHCTF1 function is more specifically tied to chromatin, nuclear pore/nuclear envelope, and kinetochore localization. additional_reference_ids: - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: PMID:27341616 supporting_text: In interphase, the ratio of nucleoplasmic versus cytoplasmic GFP signal was ~4.4-fold higher for full-length MEL-28 compared to MEL-281-956_loop2m - term: id: GO:0016604 label: nuclear body evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: >- Nuclear body is an HPA-derived localization that is not central to established AHCTF1 biology. action: MARK_AS_OVER_ANNOTATED reason: >- The mechanistic literature supports ELYS at nuclear pores/nuclear envelope, chromatin, and kinetochores. Nuclear body localization is not a demonstrated core site of AHCTF1 action and should be treated cautiously. additional_reference_ids: - PMID:17098863 - PMID:27341616 supported_by: - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - reference_id: PMID:27341616 supporting_text: Both orthologs depend on an intact beta-propeller domain and central alpha-helical domains for NPC and kinetochore organization. - term: id: GO:0031965 label: nuclear membrane evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: >- Nuclear membrane is consistent with the nuclear envelope/NPC localization of AHCTF1. action: ACCEPT reason: >- AHCTF1/ELYS localizes to the nuclear envelope and NPCs and functions during post-mitotic nuclear pore assembly. Nuclear membrane is less specific than nuclear pore but still consistent with the evidence. additional_reference_ids: - PMID:17098863 - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:27341616 qualifier: located_in review: summary: >- Nucleus is experimentally supported for MEL-28/ELYS but broad. action: KEEP_AS_NON_CORE reason: >- The paper shows conserved nuclear, NPC, chromatin, and kinetochore localization domains. Nucleus is correct as a broad location, but the core functional annotation should emphasize NPC assembly and chromatin/NPC/kinetochore sites. additional_reference_ids: - PMID:17098863 supported_by: - reference_id: PMID:27341616 supporting_text: Both orthologs depend on an intact beta-propeller domain and central alpha-helical domains for NPC and kinetochore organization. - term: id: GO:0005635 label: nuclear envelope evidence_type: EXP original_reference_id: PMID:17098863 qualifier: located_in review: summary: >- Nuclear envelope localization is directly supported by the original ELYS study. action: ACCEPT reason: >- Rasala et al. showed ELYS localizes to NPCs in the nuclear envelope and that depletion disrupts nuclear pores while other nuclear envelope markers remain comparatively intact. additional_reference_ids: - PMID:27341616 supported_by: - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - term: id: GO:0005635 label: nuclear envelope evidence_type: EXP original_reference_id: PMID:27341616 qualifier: located_in review: summary: >- Nuclear envelope localization is supported by conserved-domain analysis of MEL-28/ELYS. action: ACCEPT reason: >- The study demonstrates conserved ELYS/MEL-28 domains required for nuclear envelope/NPC localization and function, supporting nuclear envelope as a real site of action. additional_reference_ids: - PMID:17098863 supported_by: - reference_id: PMID:27341616 supporting_text: Both orthologs depend on an intact beta-propeller domain and central alpha-helical domains for NPC and kinetochore organization. - term: id: GO:0016363 label: nuclear matrix evidence_type: EXP original_reference_id: PMID:17098863 qualifier: located_in review: summary: >- Nuclear matrix was reported in the original localization work but is secondary to the NPC/chromatin mechanism. action: KEEP_AS_NON_CORE reason: >- Retain this as a historical/experimental nuclear-associated location, while recognizing that current mechanistic evidence resolves the major sites as NPC/nuclear envelope, chromatin, and kinetochore. additional_reference_ids: - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-141409 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-141422 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-141431 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-141439 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1638803 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1638821 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-2467809 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-2467811 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-2468287 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-2484822 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-375302 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5666129 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5666160 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5666169 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9615901 qualifier: located_in review: summary: >- The Reactome event is highly relevant to AHCTF1 function, but the propagated cytosol location is over-annotated. action: MARK_AS_OVER_ANNOTATED reason: >- Reactome:R-HSA-9615901 describes AHCTF1 binding chromatin and the Nup107-160 complex to seed NPC assembly. That evidence supports chromatin/nuclear pore context and nuclear pore complex assembly, not a generic cytosol cellular-component annotation. additional_reference_ids: - PMID:17098863 - PMID:27341616 - file:human/AHCTF1/AHCTF1-deep-research-falcon.md supported_by: - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md supporting_text: Human AHCTF1/ELYS is a chromatin-binding nucleoporin that seeds post-mitotic nuclear pore complex (NPC) reassembly - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9618378 qualifier: located_in review: summary: >- This downstream NPC-assembly Reactome event does not support cytosol localization for AHCTF1. action: MARK_AS_OVER_ANNOTATED reason: >- This Reactome-derived cytosol annotation appears to reflect pathway-event context rather than direct AHCTF1 localization evidence. The curated literature and UniProt record place AHCTF1/ELYS at chromatin, kinetochores, the nuclear envelope, and the nuclear pore/Nup107-160 scaffold. Any mitotic exposure to cytosol after nuclear envelope breakdown is not the informative location for this gene product. additional_reference_ids: - Reactome:R-HSA-9615901 - PMID:27341616 supported_by: - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9634169 qualifier: located_in review: summary: >- This downstream NPC-assembly Reactome event does not support cytosol localization for AHCTF1. action: MARK_AS_OVER_ANNOTATED reason: >- This Reactome-derived cytosol annotation appears to reflect pathway-event context rather than direct AHCTF1 localization evidence. The curated literature and UniProt record place AHCTF1/ELYS at chromatin, kinetochores, the nuclear envelope, and the nuclear pore/Nup107-160 scaffold. Any mitotic exposure to cytosol after nuclear envelope breakdown is not the informative location for this gene product. additional_reference_ids: - Reactome:R-HSA-9615901 - PMID:27341616 supported_by: - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9648114 qualifier: located_in review: summary: >- This Reactome-derived cytosol annotation is not an informative AHCTF1 cellular-component call. action: MARK_AS_OVER_ANNOTATED reason: >- The Reactome event concerns mitotic kinetochore/spindle-checkpoint pathway biology rather than direct localization evidence for AHCTF1 itself. AHCTF1 does have bona fide kinetochore and NPC assembly roles, but propagating the generic cytosol component from these events obscures the evidence-supported nuclear pore/chromatin/kinetochore localization. additional_reference_ids: - PMID:17098863 - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0032465 label: regulation of cytokinesis evidence_type: IMP original_reference_id: PMID:17098863 qualifier: involved_in review: summary: >- Cytokinesis regulation is experimentally supported as a depletion phenotype, but it is not the core molecular role. action: KEEP_AS_NON_CORE reason: >- ELYS depletion increased cytokinesis defects, consistent with a real cell-division consequence. The core evolved function is more specifically NPC assembly and Nup107-160/chromatin-associated scaffold recruitment; cytokinesis should be retained as a non-core phenotype/process connection. additional_reference_ids: - PMID:27341616 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: >- The extracellular exosome call comes from broad urinary-exosome proteomics and is not informative for AHCTF1 function. action: MARK_AS_OVER_ANNOTATED reason: >- This high-throughput exosome dataset identified many proteins and does not establish AHCTF1 as a functional exosome component. It conflicts with the strong nuclear pore/chromatin/kinetochore localization evidence and should not be treated as a core location. additional_reference_ids: - PMID:17098863 - PMID:27341616 supported_by: - reference_id: PMID:19056867 supporting_text: the analysis identified 1132 proteins unambiguously - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:17098863 qualifier: colocalizes_with review: summary: >- Kinetochore colocalization is directly supported for mitotic ELYS. action: ACCEPT reason: >- ELYS targets kinetochores during mitosis and this localization is part of the dual nucleoporin/kinetochore behavior described for AHCTF1/ELYS. additional_reference_ids: - PMID:27341616 supported_by: - reference_id: PMID:17098863 supporting_text: At mitosis, ELYS targets to kinetochores - reference_id: PMID:27341616 supporting_text: Both orthologs depend on an intact beta-propeller domain and central alpha-helical domains for NPC and kinetochore organization. - term: id: GO:0000785 label: chromatin evidence_type: IDA original_reference_id: PMID:17098863 qualifier: located_in review: summary: >- Chromatin localization is consistent with ELYS function as the chromatin-linked seed for post-mitotic NPC assembly. action: ACCEPT reason: >- ELYS binds chromatin during nuclear reformation and recruits the Nup107-160 subcomplex. This cellular-component annotation is supported, although a separate molecular-function chromatin binding annotation is also warranted. additional_reference_ids: - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:17098863 qualifier: located_in review: summary: >- Nuclear localization is experimentally supported but broad. action: KEEP_AS_NON_CORE reason: >- The original ELYS study supports nuclear/NPC localization. Keep the broad nucleus annotation, but do not use it as the defining core annotation when nuclear pore, chromatin, and kinetochore evidence is available. additional_reference_ids: - PMID:27341616 - file:human/AHCTF1/AHCTF1-uniprot.txt supported_by: - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Localizes to the nuclear pore complex (NPC) throughout interphase. - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:17098863 qualifier: colocalizes_with review: summary: >- Nuclear pore colocalization is a core location for AHCTF1/ELYS. action: ACCEPT reason: >- ELYS copurifies with Nup107-160, localizes to NPCs, and is required for normal nuclear pore assembly. The nuclear pore annotation is therefore central to AHCTF1 function. additional_reference_ids: - PMID:27341616 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: ELYS, a putative transcription factor, was discovered to copurify with the Nup107-160 complex - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0031080 label: nuclear pore outer ring evidence_type: IDA original_reference_id: PMID:17098863 qualifier: colocalizes_with review: summary: >- Nuclear pore outer ring colocalization is appropriate given AHCTF1 association with the Nup107-160/Y-complex scaffold. action: ACCEPT reason: >- The Nup107-160/Y-complex forms the outer-ring scaffold of the NPC, and ELYS associates with this complex during NPC assembly. The outer-ring annotation is specific and well aligned with current structural understanding. additional_reference_ids: - PMID:27016207 - Reactome:R-HSA-9615901 supported_by: - reference_id: PMID:17098863 supporting_text: ELYS, a putative transcription factor, was discovered to copurify with the Nup107-160 complex - reference_id: PMID:27016207 supporting_text: Depending on the species, it can have up to four additional proteins, Nup37, Nup43 ELYS or ELY5, and Seh1 - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - term: id: GO:0051292 label: nuclear pore complex assembly evidence_type: IMP original_reference_id: PMID:17098863 qualifier: involved_in review: summary: >- Nuclear pore complex assembly is the central experimentally supported biological process for AHCTF1/ELYS. action: ACCEPT reason: >- RNAi and assembly studies show ELYS is required for NPC formation at the reforming nuclear envelope and functions as a chromatin-linked recruiter of Nup107-160. This is the most appropriate core BP annotation. additional_reference_ids: - PMID:27341616 - Reactome:R-HSA-9615901 - file:human/AHCTF1/AHCTF1-uniprot.txt - file:human/AHCTF1/AHCTF1-deep-research-falcon.md supported_by: - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: file:human/AHCTF1/AHCTF1-uniprot.txt supporting_text: Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes - reference_id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md supporting_text: Human AHCTF1/ELYS is a chromatin-binding nucleoporin that seeds post-mitotic nuclear pore complex (NPC) reassembly - term: id: GO:0003682 label: chromatin binding evidence_type: IDA original_reference_id: PMID:27341616 qualifier: enables review: summary: >- Proposed new molecular-function annotation: AHCTF1/ELYS enables chromatin binding. action: NEW reason: >- AHCTF1 has a C-terminal chromatin-binding domain, binds chromatin during nuclear reformation, and uses that chromatin association to seed Nup107-160 recruitment and NPC assembly. This MF is more informative than generic protein binding and is directly supported by functional-domain evidence. additional_reference_ids: - PMID:17098863 - Reactome:R-HSA-9615901 - file:human/AHCTF1/AHCTF1-deep-research-falcon.md supported_by: - reference_id: PMID:27341616 supporting_text: the C-terminal end of ELYS corresponding to aa. 1851-2275 bound to metaphase chromatin - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - reference_id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md supporting_text: Human AHCTF1/ELYS is a chromatin-binding nucleoporin that seeds post-mitotic nuclear pore complex (NPC) reassembly - reference_id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md supporting_text: Kobayashi et al. provide direct structural and biochemical evidence that ELYS binds nucleosomes and map a critical basic element required for this interaction references: - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: - statement: >- UniProt subcellular-location mappings support nuclear envelope, nuclear pore, and nucleoplasm locations when consistent with experimental ELYS literature. - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: - statement: >- HPA immunofluorescence-derived locations are useful but must be interpreted against stronger ELYS NPC/chromatin/kinetochore evidence. - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: - statement: >- Automated nucleus/cytoplasm/nuclear-matrix calls are broad; nucleus is compatible, whereas cytoplasm is not a defining AHCTF1 location. - id: PMID:17098863 title: ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. findings: - statement: >- ELYS copurifies with Nup107-160, localizes to nuclear pores and kinetochores, and ELYS depletion disrupts nuclear pores and increases cytokinesis defects. - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: - statement: >- Urinary-exosome proteomics detected many proteins and does not establish AHCTF1 as a functional exosome component. - id: PMID:24315095 title: Integrated structural analysis of the human nuclear pore complex scaffold. findings: - statement: >- The human Nup107 scaffold forms reticulated NPC rings, supporting the structural context for AHCTF1 as a Nup107-160-associated NPC factor. - id: PMID:27016207 title: The Structure Inventory of the Nuclear Pore Complex. findings: - statement: >- NPCs are the principal gateway for nuclear-cytoplasmic exchange; ELYS is described as an optional/additional Y-complex-associated nucleoporin in some species. - id: PMID:27341616 title: Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation. findings: - statement: >- MEL-28/ELYS domains required for NPC, kinetochore, and chromatin localization are conserved, and the C-terminal region of human ELYS supports chromatin association. - id: Reactome:R-HSA-141409 title: Mad1 binds kinetochore findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-141422 title: MAD2 converted to an inhibitory state via interaction with Mad1 findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-141431 title: MAD2 associates with the Mad1 kinetochore complex findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-141439 title: Release of activated MAD2 from kinetochores findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-1638803 title: Phosphorylation of cohesin by PLK1 at centromeres findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-1638821 title: PP2A-B56 dephosphorylates centromeric cohesin findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-2467809 title: ESPL1 (Separase) cleaves centromeric cohesin findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-2467811 title: Separation of sister chromatids findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-2468287 title: CDK1 phosphorylates CDCA5 (Sororin) at centromeres findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-2484822 title: Kinetochore assembly findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-375302 title: Kinetochore capture of astral microtubules findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-5666129 title: CDC42:GTP recruits DIAPH2-2 to kinetochores findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-5666160 title: AURKB phosphorylates DIAPH2-2 at kinetochores findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-5666169 title: Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: Reactome:R-HSA-9615901 title: AHCTF1 (ELYS) binds chromatin and Nup107-Nup160 complex findings: - statement: >- AHCTF1/ELYS binds chromatin and the Nup107-160 complex and acts as a seeding center for NPC assembly. - id: Reactome:R-HSA-9618378 title: POM121 binds the Nup107-Nup160 complex findings: - statement: >- Downstream POM121/Nup107-160 binding is part of NPC assembly but does not provide direct AHCTF1 cytosol-localization support. - id: Reactome:R-HSA-9634169 title: POM121 and NDC1 bind the Nup93 complex findings: - statement: >- Downstream POM121/NDC1/Nup93 recruitment is part of NPC assembly but does not provide direct AHCTF1 cytosol-localization support. - id: Reactome:R-HSA-9648114 title: EML4 recruits NUDC to mitotic spindle findings: - statement: >- Reactome mitotic pathway context does not by itself justify propagating a generic cytosol location to AHCTF1. - id: file:human/AHCTF1/AHCTF1-uniprot.txt title: UniProtKB record for human AHCTF1/ELYS findings: - statement: >- Reviewed UniProt record summarizes AHCTF1 as a nuclear pore assembly factor that recruits Nup107-160 and localizes to NPCs, nuclear envelope, chromatin, and kinetochores. - id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md title: Falcon deep research review of human AHCTF1/ELYS findings: - statement: >- Falcon research summarizes AHCTF1/ELYS as a chromatin-binding nucleoporin that seeds post-mitotic NPC reassembly by recruiting the Nup107-160/Y-complex to decondensing chromosomes. - statement: >- Falcon research highlights recent literature on ELYS nucleosome binding, VAPB interaction during mitosis, chromatin anchoring at NPCs, and cancer-relevant nuclear architecture contexts. core_functions: - description: >- Chromatin-associated nuclear pore assembly factor that seeds recruitment of the Nup107-160/Y-complex scaffold to reforming nuclei after mitosis. molecular_function: id: GO:0003682 label: chromatin binding directly_involved_in: - id: GO:0051292 label: nuclear pore complex assembly locations: - id: GO:0000785 label: chromatin - id: GO:0005635 label: nuclear envelope supported_by: - reference_id: PMID:27341616 supporting_text: ELYS binding to chromatin represents the first step in the post-mitotic building of the pore - reference_id: PMID:17098863 supporting_text: depletion of ELYS by RNAi leads to severe disruption of nuclear pores in the nuclear envelope - reference_id: Reactome:R-HSA-9615901 supporting_text: AHCTF1 (ELYS, MEL-28) selectively interacts with the Nup107-160 complex and acts as a seeding center for assembly of nuclear pore complexes - reference_id: file:human/AHCTF1/AHCTF1-deep-research-falcon.md supporting_text: Human AHCTF1/ELYS is a chromatin-binding nucleoporin that seeds post-mitotic nuclear pore complex (NPC) reassembly proposed_new_terms: [] suggested_questions: - question: >- Does human AHCTF1/ELYS have separable direct requirements for NPC assembly versus kinetochore/chromosome-segregation functions in non-transformed human cells? - question: >- Which chromatin features and Nup107-160 interfaces determine AHCTF1 recruitment during post-mitotic nuclear pore assembly? - question: >- Is AHCTF1 included in proteostasis network source lists only through broad nuclear-pore/nucleocytoplasmic-transport projection, or is there direct evidence for protein homeostasis regulation? suggested_experiments: - description: >- Domain-rescue experiments in AHCTF1-depleted human cells comparing C-terminal chromatin-binding mutants and N-terminal Nup107-160-binding mutants for NPC assembly, nuclear import/export, and kinetochore phenotypes. - description: >- Quantitative proximity labeling or AP-MS across mitosis to distinguish AHCTF1 interactions with chromatin, Nup107-160/Y-complex members, and kinetochore proteins. - description: >- Proteostasis-focused stress assays after AHCTF1 perturbation that measure protein folding, ubiquitin-proteasome flux, and ER stress markers separately from secondary nuclear transport or cell-cycle defects.